Hexyl-dichloro resorcinol antiseptic



Patented May 4, 1943 HEXYL-DIGHLORO RESORCINOL ANTISEPTIO FrankW. Hartmanand Victor Schelling, Detroit,

Mich., assignors to Henry Ford Hospital, Detroit, Mich., a corporation of Michigan No Drawing. Original application November 16,

1939, Serial No. 304,734. Divided and this application September 6, 1941, SerialiNo. 409,901

1 Claim. (01. 260-623) This invention has for its principal; object to provide as a new and improved. compound a substituted derivative. of resorcinol having highly advantageous and unexpectedv properties for use primarily as an antiseptic. This application is a division of our earlier application, SerQNo. 304,-

734, filed November 16, 1939.

I The ideal antiseptic is one which musthave high bactericidal value against both cocci and bacilli and low toxicity for tissue cells both locally and generally. It must-also preferably be comparatively odorless, or at least have a non-obnoxious or non-repellent odor and be sufficiently stable so as not to lose any of its antiseptic or germicidal properties too rapidly. Likewise it is of great importance that the substance may be used in highly diluted form so as to avoid discomfort to the patient or user.

After a long period of experimentation we have succeeded in synthesizing a new compound which after extensive experimental and clinical use has shown highly unexpected properties and results. Although great antiseptic properties have been claimed for resorcinol, this compound has not proved to be entirely satisfactory or successful and numerousproposals have been made to increase the antiseptic strength of resorcinol by incorporating various substituents therein. Johnson and Lane (J. Am. Chem. Soc. 43, 348) systematically investigated the influence of a1- kyl groups on the antiseptic properties of resorcinol and showed that the antiseptic strength of resorcinol was markedly increased by the incorporation of an alkyl group and that the increase in disinfecting properties is a function of the size of the group introduced. That halogen in the ring of phenolic compounds also increases their antiseptic power has been known for a long time. While it has been known that, as stated above, an increase in disinfecting properties would be a function of size of the group introduced into the nucleus of a resorcinol compound, this would not necessarily increase the value of the compound for use as an antiseptic for it would seem that such an increase would decrease the value of the compound as an antiseptic because of an expected increased toxicity of the compound, particularly for application to burned areas, granulating surfaces and wounds generally.

After synthesizing a new compound, namely, hexyl-dichloro resorcinol, we have found after exhaustive laboratory and clinical tests that not only has the compound shown surprisingly and highly unexpected effectiveness against bacteria of both the cocci and bacilli group, but remarkably low toxicity locally with low systemic toxicity.

Starting with chloro-resorcinol (I-B-dihydroXy-4-chlorobenzene, Eastman) this is further chlorinated with sulfuryl-chloride $02012 according tothe method described by Moore, Day, and Suter (J. Am. Chem. Soc. 56, 2456, 1934) the reaction being graphically represented as follows:

The resulting 4-6-dichloro-resorcinol is then treated with caproic acidchloride and subjected to heat to form the 4-6-dichlororesorcinol-dicaproylester.

This compound when distilled in a high vacuum is a clear oil. The Rosenmund and Schnurr rearrangement reaction with A1C13 (Ann. Chem, 460, 56, 1928) was applied to the diester above formed. Advantage was taken from the observation of Stoughton, Baltzly and Bass (J. Am. Chem. Soc. 56, 2007, 1934) that the second alkyl group of the diester in the rearrangement of dihydroxibenzenes can be included in the reaction by adding one mol. of the free phenol. The proportion of the reacting substances in this case were accordingly as follows: 1 mol. of dichlororesorcinol-dicaproylester, 1 mol. dichloro-resorcinol and 2.2 mols. anhydrous AlCls.

The resulting ketone (2-hexylyl-4-6-dichlororesorcinol) is distilled in high vacuum (3. P. ISO-185 C.) It is a yellowish oil which easily crystallizes in the cold (M. P. 119-120). Thev ketone is reduced with amalgamated zinc and hydrochloric acid I HCI according to Clemmensen to the corresponding alkyl compound 4-6-dichloro-2-hexyl-resorcinol The resulting hexyl-dichloro-resorcinal distills in high vacuum at 143-146" C, It is a slightly yellowish liquid which on cooling crystallizes to a white mass (M. P. 36-38).

The compound above has been found highly effective in combination with small amounts of acid such, for example, as hydrochloric acid, so that the pH would be between 2 and 3, as this results in a marked highly unexpected increase in the effectiveness and the relatively low pH is preferred because it adds but little to the tissue toxicity. Used in combination with tannic acid, which as is now well known has proven highly effective in the treatment of burns, and keeping the pH as above outlined, very remarkable results have been achieved. It has been found that r a dilution highly effective in ten minutes, as follows has been obtained:

gg f Selle & Lazarus method T Highest dilution lnlls in 10 Tissue min. but not in 6 min. culture Tmcity A B 0 01A 01B S. aureus E. typhi plus 36% 1161 as, 000 i so, 000

hereinbeforedescribed may be applied directly withtannic acid in the treatment of burns and when the pH is kept within the limits hereinbefore set forth, the tannic acid and carbocyclic antiseptic have marked, and highly desirable, synergistic properties.

We claim: A new compound having the formula 01- CHI(CHI)4CHZ FRANK W. HARTMAN. VICTOR SCHELLING. 

